SANT-1

Catalog No.S7092 Batch:S709201

Technical Data

Formula

C₂₃H₂₇N₅

Molecular Weight

373.49

CAS No.

304909-07-7

Solubility (25°C)*

In vitro

DMSO

21 mg/mL (56.22 mM)

Ethanol

20 mg/mL (53.54 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	1.05mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 21 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil	1.05mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 21 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

SANT-1 directly binds to Smoothened (Smo) receptor with K_d of 1.2 nM and inhibits Smo agonist effects with IC50 of 20 nM.

Targets

Smoothened receptor ^[1]

1.2 nM(Kd)

In vitro

SANT-1 inhibits wild type and oncogenic Smo with equal potency. SANT-1 counteracts SAG-induced pathway activation in Shh-LIGHT2 cells. SANT-1 is able to block BODIPY-cyclopamine binding to Smo-expressing cells, but SANT-1 is unable to inhibit completely this association to background levels. This suggests that their interactions with Smo may alter its affinity for cyclopamine rather than compete directly for cyclopamine binding. SANT-1 blocks pathway activation in SmoA1-LIGHT2 cells with potencies similar to those observed in the Shh-LIGHT2 assay. SANT-1 has disparate inhibitory activities in the Shh-LIGHT2 and BODIPY-cyclopamine assays and is unusually potent at blocking SAG-mediated pathway activation.^[1]

SANT-1 efficiently inhibited cyclopamine- and jervine- induced translocation of Smo to the primary cilium. SANT-1 inhibits PKA stimulation of Smo trafficking to the proximal cilium.^[2]

When combined HDAC inhibitor SAHA, SANT-1 is able to suppress cellular proliferation and colony formation of Gemcitabine-resistant pancreatic adenocarcinoma cell lines Panc-1 and BxPC-3. ^[3]

Features

Attenuates SAG stimulation of Shh-LIGHT2 cells to a greater extent relative to other antagonists.

Protocol (from reference)

Kinase Assay:^{^[1]}	Small Molecule Screens for Hh Pathway Modulators Shh-N (N-terminal fragment of Shh without cholesterol modification)-conditioned medium is obtained from an HEK 293 cell line stably transfected with Shh-N expression and neomycin resistance constructs. The Shh-N-producing HEK 293 cells are grown to 80% confluency in DMEM containing 10% (vol/vol) FBS and 400 μg/ml G418. The medium then is replaced with DMEM containing 2% (vol/vol) FBS, and after 1 day of growth, the medium is collected and filtered through a 0.22-μm membrane. Control medium is obtained from HEK 293 cells. Shh-LIGHT2 cells are then cultured to confluency in 96-well plates and treated with the small molecules (0.714 μg/mL; ≈2 μM compound in each well) in the presence of either Shh-N-conditioned medium or HEK 293 control medium (1:25 dilution into DMEM containing 0.5% bovine calf serum). After incubating the treated cells for 30 h at 37°C, cellular firefly and Renilla luciferase activities are measured.
Animal Study:^{^[5]}	Animal Models Swiss albino male mice Dosages 3.3 mg/kg Administration i.p.

Kinase Assay:^{^[1]}

Small Molecule Screens for Hh Pathway Modulators
Shh-N (N-terminal fragment of Shh without cholesterol modification)-conditioned medium is obtained from an HEK 293 cell line stably transfected with Shh-N expression and neomycin resistance constructs. The Shh-N-producing HEK 293 cells are grown to 80% confluency in DMEM containing 10% (vol/vol) FBS and 400 μg/ml G418. The medium then is replaced with DMEM containing 2% (vol/vol) FBS, and after 1 day of growth, the medium is collected and filtered through a 0.22-μm membrane. Control medium is obtained from HEK 293 cells. Shh-LIGHT2 cells are then cultured to confluency in 96-well plates and treated with the small molecules (0.714 μg/mL; ≈2 μM compound in each well) in the presence of either Shh-N-conditioned medium or HEK 293 control medium (1:25 dilution into DMEM containing 0.5% bovine calf serum). After incubating the treated cells for 30 h at 37°C, cellular firefly and Renilla luciferase activities are measured.

Animal Study:^{^[5]}

Animal Models
Swiss albino male mice
Dosages
3.3 mg/kg
Administration
i.p.

References

Customer Product Validation

: , , Oncotarget, 2017, 8(40): 67891-67903

Selleck's SANT-1 has been cited by 14 publications

CNPY4 inhibits the Hedgehog pathway by modulating membrane sterol lipids [ Nat Commun, 2022, 13(1):2407]	PubMed: 35504891
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7]	PubMed: 34997030
Hedgehog pathway is negatively regulated during the development of Drosophila melanogaster PheRS-m (Drosophila homologs gene of human FARS2) mutants [ Hum Cell, 2022, 10.1007/s13577-022-00796-0]	PubMed: 36205831
Microengineered Multi-Organoid System from hiPSCs to Recapitulate Human Liver-Islet Axis in Normal and Type 2 Diabetes [ Adv Sci (Weinh), 2021, e2103495]	PubMed: 34951149
Generation of functional human thymic cells from induced pluripotent stem cells [ J Allergy Clin Immunol, 2021, S0091-6749(21)01141-6]	PubMed: 34331993
One-Step Generation of Aqueous-Droplet-Filled Hydrogel Fibers as Organoid Carriers Using an All-in-Water Microfluidic System [ ACS Appl Mater Interfaces, 2021, 13(2):3199-3208]	PubMed: 33405509
Compound Tongluo Decoction inhibits endoplasmic reticulum stress-induced ferroptosis and promoted angiogenesis by activating the Sonic Hedgehog pathway in cerebral infarction [ J Ethnopharmacol, 2021, S0378-8741(21)00863-1]	PubMed: 34536518
FGF2 Inhibits Early Pancreatic Lineage Specification during Differentiation of Human Embryonic Stem Cells [ Cells, 2020, 9(9):E1927]	PubMed: 32825270
GATA6-AS1 Regulates GATA6 Expression to Modulate Human Endoderm Differentiation [ Stem Cell Reports, 2020, S2213-6711(20)30291-5]	PubMed: 32795420
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004]	PubMed: 31740922

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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